Genetic variants in telomerase-associated protein 1 are associated with telomere damage in PAH-exposed workers

Duan, Xiaoran; Wang, Hongmei; Yang, Yongli; Wang, Pengpeng; Liu, Bin; Wei, Wan; Yao, Wu; Zhou, Xiaoshan; Zhao, Jie; Wang, Wei

doi:10.1016/j.ecoenv.2021.112558

Cited by 7 publications

(4 citation statements)

References 28 publications

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“…Telomerase-associated protein 1(TEP1) is a constitute of ribonucleoprotein complex which is responsible for the activity of telomerase ( Duan et al., 2021 ). In a Drosophila glioma model, the downregulation of TEP1 reduced the activity of Yki and curtailed the growth of glioma ( Gangwani et al., 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Multiomics and bioinformatics identify differentially expressed effectors in the brain of Toxoplasma gondii infected masked palm civet

Yuan,

Jiang,

Zhang

et al. 2023

Front. Cell. Infect. Microbiol.

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IntroductionThe masked palm civet (Paguma larvata) serves as a reservoir in transmitting pathogens, such as Toxoplasma gondii, to humans. However, the pathogenesis of T. gondii infection in masked palm civets has not been explored. We studied the molecular changes in the brain tissue of masked palm civets chronically infected with T. gondii ME49.MethodsThe differentially expressed proteins in the brain tissue were investigated using iTRAQ and bioinformatics.ResultsA total of 268 differential proteins were identified, of which 111 were upregulated and 157 were downregulated. KEGG analysis identified pathways including PI3K-Akt signaling pathway, proteoglycans in cancer, carbon metabolism, T-cell receptor signaling pathway. Combing transcriptomic and proteomics data, we identified 24 genes that were differentially expressed on both mRNA and protein levels. The top four upregulated proteins were REEP3, REEP4, TEP1, and EEPD1, which was confirmed by western blot and immunohistochemistry. KEGG analysis of these 24 genes identified signaling cascades that were associated with small cell lung cancer, breast cancer, Toll-like receptor signaling pathway, Wnt signaling pathways among others. To understand the mechanism of the observed alteration, we conducted immune infiltration analysis using TIMER databases which identified immune cells that are associated with the upregulation of these proteins. Protein network analysis identified 44 proteins that were in close relation to all four proteins. These proteins were significantly enriched in immunoregulation and cancer pathways including PI3K-Akt signaling pathway, Notch signaling pathway, chemokine signaling pathway, cell cycle, breast cancer, and prostate cancer. Bioinformatics utilizing two cancer databases (TCGA and GEPIA) revealed that the four genes were upregulated in many cancer types including glioblastoma (GBM). In addition, higher expression of REEP3 and EEPD1 was associated with better prognosis, while higher expression of REEP4 and TEP1 was associated with poor prognosis in GBM patients.DiscussionWe identified the differentially expressed genes in the brain of T. gondii infected masked palm civets. These genes were associated with various cellular signaling pathways including those that are immune- and cancer-related.

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Section: Discussionmentioning

confidence: 99%

Multiomics and bioinformatics identify differentially expressed effectors in the brain of Toxoplasma gondii infected masked palm civet

Yuan,

Jiang,

Zhang

et al. 2023

Front. Cell. Infect. Microbiol.

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“…TEP1 is responsible for RNA and protein binding and is involved in the regulation of telomere length [ 22 , 23 ]. TEP1 is thought to function as a structural protein by binding to TERC and acting as a regulatory subunit to mediate the interaction of telomerase with other molecules [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

“…In this study, we aimed to determine the influence of the TEP1 gene SNP rs1760904 and rs1713418 on the occurrence of MS. The SNP rs1760904 A > G is located in the exon region of the TEP1 gene [ 23 , 26 ]. Rs1760904 is a nonsynonymous SNP that causes a proline-to-serine substitution (Ser1195Pro) that may affect the TEP1 structure and telomerase [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

The Influence of TEP1 and TERC Genetic Variants on the Susceptibility to Multiple Sclerosis

Rumšaitė,

Gedvilaitė,

Balnytė

et al. 2023

JCM

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Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. According to recent studies, cellular senescence caused by telomere shortening may contribute to the development of MS. Aim of the study: Our aim was to determine the associations of TEP1 rs1760904, rs1713418, TERC rs12696304, rs35073794 gene polymorphisms with the occurrence of MS. Methods: The study included 200 patients with MS and 230 healthy controls. Genotyping of TEP1 rs1760904, rs1713418 and TERC rs12696304, rs35073794 was performed using RT-PCR. The obtained data were analysed using the program “IBM SPSS Statistics 29.0”. Haplotype analysis was performed using the online program “SNPStats”. Results: The TERC rs12696304 G allele of this SNP is associated with 1.4-fold lower odds of developing MS (p = 0.035). TERC rs35073794 is associated with approximately 2.4-fold reduced odds of MS occurrence in the codominant, dominant, overdominant, and additive models (p < 0.001; p < 0.001; p < 0.001; p < 0.001, respectively). Haplotype analysis shows that the rs1760904-G—rs1713418-A haplotype is statistically significantly associated with 1.75-fold increased odds of developing MS (p = 0.006). The rs12696304-C–rs35073794-A haplotype is statistically significantly associated with twofold decreased odds of developing MS (p = 0.008). In addition, the rs12696304-G—rs35073794-A haplotype was found to be statistically significantly associated with 5.3-fold decreased odds of developing MS (p < 0.001). Conclusion: The current evidence may suggest a protective role of TERC SNP in the occurrence of MS, while TEP1 has the opposite effect.

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“…TEP1 is responsible for RNA and protein binding and is involved in the regulation of telomere length [22,23]. TEP1 is thought to function as a structural protein by binding to TERC and acting as a regulatory subunit to mediate the interaction of telomerase with other molecules [24].…”

Section: Introductionmentioning

confidence: 99%

Do TEP1 and TERC Have an Impact on Multiple Sclerosis Manifestation?

Rumsaite,

Gedvilaite,

Balnyte

et al. 2023

Preprint

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Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. According to recent studies, cellular senescence caused by telomere shortening may contribute to the development of MS. Aim of the study: to determine the associations of TEP1 rs1760904, rs1713418, TERC rs12696304, rs35073794 gene polymorphisms with the occurrence of MS. Methods: The study included 200 patients with MS and 230 healthy controls. Genotyping of TEP1 rs1760904, rs1713418 and TERC rs12696304, rs35073794 was performed using RT-PCR. Statistical analysis of the obtained data was performed using the program "IBM SPSS Statistics 29.0". Haplotype analysis was performed using the online program "SNPStats". Results: The TERC rs12696304 G allele of this SNP is associated with a 1.4-fold lower odds of developing MS (p=0.035). TERC rs35073794 is associated with an approximately 2.4-fold reduced odds of MS occurrence in the codominant, dominant, overdominant, and additive models (p < 0.001; p < 0.001; p < 0.001; p < 0.001, respectively). Haplotype analysis shows that the rs1760904-G - rs1713418-A haplotype is statistically significantly associated with a 1.75-fold increased odds of developing MS (p=0.006). The rs12696304-C - rs35073794-A haplotype is statistically significantly associated with a 2-fold decreased odds of developing MS (p=0.008). In addition, the rs12696304-G - rs35073794-A haplotype was found to be statistically significantly associated with a 5.3-fold decreased odds of developing MS (p&lt;0.001). Conclusion: Current evidence may suggest a protective role of TERC SNP in the occurrence of MS, while TEP1 has the opposite effect.

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Genetic variants in telomerase-associated protein 1 are associated with telomere damage in PAH-exposed workers

Cited by 7 publications

References 28 publications

Multiomics and bioinformatics identify differentially expressed effectors in the brain of Toxoplasma gondii infected masked palm civet

Multiomics and bioinformatics identify differentially expressed effectors in the brain of Toxoplasma gondii infected masked palm civet

The Influence of TEP1 and TERC Genetic Variants on the Susceptibility to Multiple Sclerosis

Do TEP1 and TERC Have an Impact on Multiple Sclerosis Manifestation?

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